This proposal requests partial funding to support the 2013 Gordon Research Conference on Three- Dimensional Electron Microscopy of Macromolecules (3DEM), continuing this most successful series. Three- dimensional electron microscopy (3DEM) offers unique insights into the structure and mechanisms of biological macromolecules and their assemblies in health and disease. Unlike any other technique in structural and molecular cell biology, 3DEM spans an extraordinarily wide range, from near-atomic detail of membrane proteins and important pathogens such as viruses and amyloid fibrils, to cell organelles such as the ribosome and proteosome, and to whole cells. Most protein in the cell is assembled into complexes, and EM is one of the most important tools for studying macromolecular complexes. It provides a great deal of complementarity with techniques such as x-ray crystallography and NMR, on the one hand, and light microscopy, on the other. Continual advances have been made in this field, from hardware (such as better detectors) to software (such as new algorithms for processing images), and these advances are the main focus for this conference. The impact of the preceding 18 meetings has been such that the 3DEM community has come to regard this Gordon Conference as the most important scientific event in the field. The next 3DEM GRC will be held in New Hampshire in June 2013.